D. Klionsky
Cell Death & Differentiation, 2020
Two years ago, I was asked to give a talk about autophagy and cancer. That seemed reasonable enough, but as a researcher who works primarily with yeast, I needed to do some extensive reading of the literature. Sure, I knew, or thought I knew, the basics about this topic, but this talk was for students, who might assume that what I said was actually correct, so I wanted to get it right. Yet, the more I read about the subject the less clear it became. The problem was not with any individual study, but rather trying to figure out what the overall “take home” message might be. One problem has to do with the fact that cancer studies generally are not carried out using yeast, and more’s the pity. Although there are indeed different yeast strains, they are still fairly similar, at least compared with the differences inherent in other model systems. With cancer studies, for example, people use all sorts of cell lines. For those of us who are not well versed in mammalian cell lines, it can be difficult to sort out the relevance or to make comparisons. Add to this the fact that researchers are studying various types of cancer, and you have a real problem on your hands. The final complication when it comes to having a clear understanding of autophagy and cancer? Not all of these studies agree with one another. So, what could I do for my talk? My first solution was to extend the topic from autophagy and cancer to autophagy and disease. Now, you may think that broadening the coverage to all diseases would only make that situation worse. However, this way I could pick and choose. I still decided to cover the highlights of autophagy and cancer, although that is not an easy task in and of itself—do you have any idea how many papers have already been published on this topic? Let’s just say quite a few. One point I did take away from my reading, which I am sure you are already familiar with, is that the relationship between autophagy and cancer is complex. Thus, from a clinical perspective, the decision as to whether to inhibit or stimulate autophagy to augment an anticancer treatment depends on the type of cancer and its stage of progression. During my talk, this allowed me to emphasize the importance of understanding how autophagy is regulated (after all, no reason not to get in a little promotion for my own research interests). I concluded my discussion of cancer by noting that there were certainly controversies in this field, which means that more research is needed. Then, on to other diseases. I have to say that one of the issues I encountered in my reading is that, despite all of the research, in many cases the molecular mechanism relating autophagy to a particular disease may not be known. This is not stated as a criticism, simply as a fact. I mean that it would have been neat to be able to present all these examples of how and why autophagic dysfunction contributes to a disease, but we do not always know the answer. That should not be surprising considering that the molecular analysis of autophagy is still in its infancy. Nonetheless, for my purposes I tried to focus on diseases where something was known about the molecular basis relative to autophagy. This still provides a wide range of options where there are clear mechanistic connections such as for some aspects of xenophagy as part of the immune response, and mitophagy with regard to its role in neurodegeneration. But, how about heart disease? Lung disease? Liver disease? Macular degeneration? Diabetes? Kidney disease? Myopathies? Whoa. At this point, you may be wondering about the “take home” message of this introduction. That is quite simple. The topic of autophagy is huge. Whether you are interested in autophagic dysfunction and its relation to disease, or the role of autophagy in normal physiological processes, there are some issues you need to deal with: (1) There is often a vast literature—the “explosion” of research in the field of autophagy has led to a corresponding number of papers. (2) The field is rapidly evolving, making it difficult to keep up. (3) As a result of items 1 and 2, there are many uncertainties * Daniel J. Klionsky klionsky@umich.edu
Cited by 19 publications.
Field of study: Biology